GlcNAc 2 epimerase

Nonlysosomal sialuria (also called French-type sialuria) is characterized by massive excretion of free sialic acid in urine. Only four patients have been described. The defect is caused by a defective feedback inhibition of UDP-GlcNAc-2-epimerase... 

GNE UDP-GlcNAc 2-epimerase/ManNAc 6-kinase GDP guanidine diphosphate hEBD human embryoid body-derived... 

Figure 10 The sialoside biosynthetic pathway in eukaryotic cells A, UDP-GlcNAc-2-epimerase B, ManNAc-6-kinase C, Neu5Ac-9-P04 synthase D, NeuSAc-b-POj phosphatase E, CMP-Neu5Ac-synthetase F, sialyltransferase. Enzymes A and B function together as a bifunctional enzyme.

Keppler, O. T. Hinderlich, S. Langner, J. Schwartz-Aibiez, R. Reutter, W. Pawlita, M., UDP-GlcNAc 2-epimerase a regulator of cell surface sialylation. Science 1999,284, (5418), 1372-6. 

Figure 11.1 The sialic acid biosynthetic pathway. Sialic acid biosynthesis occurs within the cytosol and is governed by the bifunctional enzyme GNB, which has two domains that possess enzymatic activities UDP-GlcNAc 2-epimerase and ManNAc kinase. Synthesis starts with the epimerization of UDP-GlcNAc to ManNAc by UDP-GlcNAc 2-epimerase after the release of UDP in a two-stage process. Phosphorylation of ManNAc is catalyzed by ManNAc kinase, but in some hyposialylated cells this canbe done by GlcNAc kinase. Subsequent steps lead to formation of free...

Penner J, Mantey LR, Elgavish S et al. (2006) Influence of UDP-GlcNAc 2-Epimerase/ManNAc kinase mutant proteins on hereditary inclusion body myopathy. Biochemistry AS, 2968-2977. 

Kurochkina N, Yardeni T, Huizing M. (2010) Molecular modeling of the bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase and predictions of structural effeds of mutations assodated with HIBM and sialuria. Glycobiology 20, 322-337. 

Luchansky SJ, Yarema KJ, Takahashi S, Bertozzi CR. (2003) GlcNAc 2-epimerase can serve a catabolic role in sialic acid metabolism. J Biol Chem 278, 8035-8042. 

Krause S, Hinderlich S, Amsili S et al. (2005) Localization of UDP-GlcNAc 2-epimerase/ManAc kinase (GNB) in the Golgi complex and the nucleus of mammalian cells. Exp Cell Res 304, 365-379. 

Wang Z, Sun Z, Li AV, Yarema KJ. (2006) Roles for UDP-GlcNAc 2-epimerase/ManNAc 6-kinase outside of sialic add biosynthesis modulation of sialyltrans-ferase and BiP expression, GM3 and GD 3 biosynthesis, proliferation, and apoptosis, and ERKl/2 phosphorylation. JEM Chem 281(37), 27016-27028. 

UDP-GlcNAc 2 epimerase UDP-GlcNAc ManNAc + UDP CMP-Neu5Ac cytosol... 

Long term hormonal control functions in the expression of enzyme concentrations and de novo acceptor molecule synthesis in the case of sialyltransfer reactions. Examples in development have been cited (sections II.2, II. 3, and III. 10), and the regenerating liver has proved valuable in studies of this kind, e.g. UDP-GlcNAc 2-epimerase (Okubu et al. 1976, Okamoto and Akamatsu 1980). Elevation of enzyme concentration could be shown to be a function of de novo protein synthesis. Study of hormone effects (oestrogen, progesterone) on sialyltransferase activity and glycosidically linked sialic acid levels in the cervical cyclic phenomena have been reported (Moghissi and Syner 1976, Chantler and Debruyn 1977, Hatcher et al. 1977, Nasir-ud-Din et al. 1979, Wolf et al. 1980). Similar effects have been demonstrated in rat endometrium (Nelson et al. 1975). 

UDP-GlcNAc-2-epimerase activity [24], has not been detected in many tissues other than liver suggesting that there may be alternate routes for sialic acid formation. Recently the gene for the epimerase has been used as a probe for Northern blot analysis of mRNA from various tissues. The lack of an epimerase mRNA signal from many of the tissues confirms the observations of earlier enzymatic studies [25, 26]. 

Genes needed to supplement or GlcNAc-2-epimerase or UDP- A-acetylglucosminyltransferase II a-mannosidase I and II and/or... 

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